The Diabetes in Early Pregnancy Project was designed 1) to examine the relationship between maternal diabetic control during organogenesis and malformations in the offspring, and to identify, if possible, a specific teratogenic factor or factors in the diabetic metabolic state; and 2) to compare early fetal loss rates in women with diabetes and in non-diabetic control subjects. We found that diabetic women who came into care before the period of organogenesis achieved better results than those who came in later; but their results were still poorer than for non-diabetic control subjects. Differences in maternal glucose levels during organogenesis did not explain the malformations in the offspring of the women who were followed throughout pregnancy. These results suggest that women who enter late (and were not under medical supervision during organogenesis) probably had poor control. This resulted in malformations due to hyperglycemia or related factors. The diabetic group entering early strongly suggests that other teratogenic mechanisms were present. Regarding early fetal losses, we found that diabetic women in good metabolic control were at no higher risk for spontaneous abortion than control women; the risk of loss increased dramatically as diabetic control worsened; and the overall risk of losing a pregnancy was lower than expected, only 16%. Since these primary analyses were completed, a number of related studies have been completed (see previous reports). At present, issues relating to minor malformations, metabolic factors, and retinopathy are being addressed. Blood specimens at the Sansum Foundation are being assayed for glycosylated protein to examine the relationship between intermediate term control and malformations although funding problems have slowed progress. The National Eye Institute has joined us in an analysis of retinal photographs taken at the beginning and end of pregnancy to assess the effect of pregnancy on retinopathy. The University of Tennessee will measure blood levels of anti-sperm antibodies and anti-phospholipid antibodies in relation to spontaneous abortion.